The Co-chaperone Sba1 connects the ATPase reaction of Hsp90 to the progression of the chaperone cycle
| Autor: | Klaus Richter, Johannes Buchner, Stefan Walter |
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| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular Saccharomyces cerevisiae Proteins Dimer Isomerase Saccharomyces cerevisiae Fungal Proteins chemistry.chemical_compound Cyclophilins Structural Biology ATP hydrolysis polycyclic compounds Prolyl isomerase HSP90 Heat-Shock Proteins Molecular Biology Heat-Shock Proteins Adenosine Triphosphatases biology Hydrolysis Hsp90 Co-chaperone Cross-Linking Reagents chemistry Biochemistry Chaperone (protein) biology.protein Biophysics Signal transduction Dimerization Cyclophilin D Molecular Chaperones Protein Binding |
| Zdroj: | Journal of molecular biology. 342(5) |
| ISSN: | 0022-2836 |
| Popis: | The molecular chaperone Hsp90 mediates the ATP-dependent activation of a large number of proteins involved in signal transduction. During this process, Hsp90 was found to associate transiently with several accessory factors, such as p23/Sba1, Hop/Sti1, and prolyl isomerases. It has been shown that ATP hydrolysis triggers conformational changes within Hsp90, which in turn are thought to mediate conformational changes in the substrate proteins, thereby causing their activation. The specific role of the partner proteins in this process is unknown. Using proteins from Saccharomayces cerevisiae , we characterized the interaction of Hsp90 with its partner protein p23/Sba1. Our results show that the nucleotide-dependent N-terminal dimerization of Hsp90 is necessary for the binding of Sba1 to Hsp90 with an affinity in the nanomolar range. Two Sba1 molecules were found to bind per Hsp90 dimer. Sba1 binding to Hsp90 resulted in a decreased ATPase activity, presumably by trapping the hydrolysis state of Hsp90 ATP. Ternary complexes of Hsp90 Sba1 could be formed with the prolyl isomerase Cpr6, but not with Sti1. Based on these findings, we propose a model that correlates the ordered assembly of the Hsp90 co-chaperones with distinct steps of the ATP hydrolysis reaction during the chaperone cycle. |
| Databáze: | OpenAIRE |
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